Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial

Sabrina Paganoni, Suzanne Hendrix, Samuel P. Dickson, Newman Knowlton, James D. Berry, Michael A. Elliott, Samuel Maiser, Chafic Karam, James B. Caress, Margaret Ayo Owegi, Adam Quick, James Wymer, Stephen A. Goutman, Daragh Heitzman, Terry D. Heiman-Patterson, Carlayne Jackson, Colin Quinn, Jeffrey D. Rothstein, Edward J. Kasarskis, Jonathan KatzLiberty Jenkins, Shafeeq S. Ladha, Timothy M. Miller, Stephen N. Scelsa, Tuan H. Vu, Christina Fournier, Kristin M. Johnson, Andrea Swenson, Namita Goyal, Gary L. Pattee, Suma Babu, Marianne Chase, Derek Dagostino, Meghan Hall, Gale Kittle, Mathew Eydinov, Joseph Ostrow, Lindsay Pothier, Rebecca Randall, Jeremy M. Shefner, Alexander V. Sherman, Eric Tustison, Prasha Vigneswaran, Hong Yu, Joshua Cohen, Justin Klee, Rudolph Tanzi, Walter Gilbert, Patrick Yeramian, Merit Cudkowicz

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background Coformulated sodium phenylbutyrate/taurursodiol (PB/TURSO) was shown to prolong survival and slow functional decline in amyotrophic lateral sclerosis (ALS). Objective Determine whether PB/TURSO prolonged tracheostomy/ventilation-free survival and/or reduced first hospitalisation in participants with ALS in the CENTAUR trial. Methods Adults with El Escorial Definite ALS ≤18 months from symptom onset were randomised to PB/TURSO or placebo for 6 months. Those completing randomised treatment could enrol in an open-label extension (OLE) phase and receive PB/TURSO for ≤30 months. Times to the following individual or combined key events were compared in the originally randomised treatment groups over a period spanning trial start through July 2020 (longest postrandomisation follow-up, 35 months): death, tracheostomy, permanent assisted ventilation (PAV) and first hospitalisation. Results Risk of any key event was 47% lower in those originally randomised to PB/TURSO (n=87) versus placebo (n=48, 71% of whom received delayed-start PB/TURSO in the OLE phase) (HR=0.53; 95% CI 0.35 to 0.81; p=0.003). Risks of death or tracheostomy/PAV (HR=0.51; 95% CI 0.32 to 0.84; p=0.007) and first hospitalisation (HR=0.56; 95% CI 0.34 to 0.95; p=0.03) were also decreased in those originally randomised to PB/TURSO. Conclusions Early PB/TURSO prolonged tracheostomy/PAV-free survival and delayed first hospitalisation in ALS. Trial registration number NCT03127514; NCT03488524.

Original languageEnglish (US)
Pages (from-to)871-875
Number of pages5
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume93
Issue number8
DOIs
StatePublished - Aug 1 2022

Keywords

  • ALS
  • MOTOR NEURON DISEASE
  • NEUROMUSCULAR
  • RANDOMISED TRIALS

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health

Fingerprint

Dive into the research topics of 'Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial'. Together they form a unique fingerprint.

Cite this